Alkylating chemotherapy agents

Alkylating agents were one of the earliest classes of drugs used to treat cancer. They disrupt DNA structure and formation to cause irreparable DNA damage in cancer cells which ultimately leads to cell death.

The five major categories of alkylating agents are:

Nitrogen mustards- e.g. mechlorethamine, ifosfamide, melphalan, chlorambucil, estramustine and cyclophosphamide

Nitrosoureas- e.g. streptozocin, carmustine, bendamustine and lomustine

Alkyl sulfonates- e.g. busulfan and treosulfan

Triazines- e.g. dacarbazine and temozolomide

Ethylenimines- e.g. thiotepa and altretamine

Some cancers can develop resistance to alkylating agents, by utilising the activity of the enzyme O-6-methylguanine-DNA methyltransferase (MGMT) to repair the alkylating agent-induced DNA damage. For example, MGMT is able to repair methyl group damage on guanine nucleotides in DNA caused by temozolomide, thus negating its antineoplastic effect.